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【Objective】 To evaluate the role of anti-HBc detection in current blood screening strategy by the follow-up of repeated donors with antibody to hepatitis B virus core antigen. 【Methods】 Plasma samples were collected randomly from Dalian Blood Center. to test anti-HBc(dual reagents) and anti-HBs via ELISA. The re-donation of eligible donors who were anti-HBc+ and donors reactive to HBV detection were followed up. 【Results】 A total of 1 291 plasma samples were collected randomly from May 2017 to March 2018, among which 405 samples(31.4%)were anti-HBc+. The median age of anti-HBc+ group was observed much higher than that of anti-HBc-group (39 vs 31 years old) (P0.05). Among the 405 anti-HBc+ donors, 3 donors were OBI (0.7%), of which one was screened out in second donation. No HBV DNA was detected out in 3 OBI cases. 【Conclusion】 Although anti-HBc detection is not suitable in blood screening currently, it is of great value in the assessment of blood donor re-entry for HBV reactive donors in blood screening due to the high anti-HBc prevalence among blood donors.
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【Objective】 To analyze the characteristics of gene mutation in S region of blood donors with occult hepatitis B virus infection (OBI) in Huzhou area. 【Methods】 A total of 60 107 blood samples in Huzhou between October 2018 and June 2020 were collected by our blood station. Among them, 52 samples were NAT, yield and their epidemiological characteristics were analyzed. Twenty-seven OBI out of the 52 NAT yield samples were included in experimental group. Other eight HBV-infected individuals with positive HBsAg, core antibody (anti-HBc) and HBV-DNA were selected as positive control. Liver function and 5 serological markers of HBV were compared between the two groups, and HBV genotypes and amino acid mutation in S region in the two groups were analyzed. 【Results】 The number of NAT-yield samples were different by gender, age, and educational background (P0.05). Surface antigen (HBsAg) in the experimental group was significantly lower than that in the control group, while surface antibody (anti-HBs) and e antibody (anti-HBe) were significantly higher than those in the control group (P<0.05). Twenty sequences in S region were obtained from the experimental group, including 4 in S region and 16 in preSS region; 16 cases with type C and 4 cases with type B. 【Conclusion】 The follow-up of NAT-yield blood donors in Huzhou area should be conducted. Compared with HBV infected individuals with positive HBsAg, anti-HBc and HBV-DNA, those with OBI have a higher gene mutation rate in S region.
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【Objective】 To investigate the prognosis of blood donors with occult hepatitis B virus infection (OBI) by long-term follow-up and repeated testing of HBsAg and HBV DNA. 【Methods】 From January 1, 2010 to December 31, 2020, voluntary blood donors were screened by both serological and viral nucleic acid(NAT) testing, then samples were further confirmed as HBV DNA positive by manual nested-PCR amplification.A total of 306 cases were detected as HBsAg negative /HBV DNA positive, then followed-up for a long time and re-examined of HBsAg and HBV DNA to confirm whether they had infected with OBI.The prognosis of patients with OBI who experienced long-term immunization was determined by repeated testing. 【Results】 A total of 306 HBsAg negative/ HBV DNA positive blood donors had been followed up, and 40(13.07%, 40/306) were recalled frequently for re-examination.Among them, 90%(36/40), 57.5%(23/40), 40% (16/40)were anti-HBc + , anti-HBs + and anti-HBe + , respectively, and 50%(20/40), 40%(16/40), 7.5%(3/40) and 2.5% (1/40)were anti-HBs+ / anti-HBc + , anti-HBc + / anti-HBs -, anti-HBc -/ anti-HBs + and anti-HBc -/ anti-HBs -, respectively.Those 40 blood donors were followed-up for 1-13 times, with the duration of 8-108 months (0.6~9 years).1 donor (2.5%) was followed-up less than 1 year, 11 (27.5%)>1 year and ≤3 years, 23 (57.5%) 23(57.5%)>3 years and ≤5 years, and 5 (12.5%) for more than 5 years.After long-term following up and repeated testing, 50%(20/40)of OBI blood donors turned negative for HBV DNA (HBsAg negative / HBV DNA negative), 42.5% (17/40)were confirmed as OBI infection (HBsAg negative / HBV DNA positive), and 7.5%(3/40) were hard to determine (after repeated testing, the results were either positive or negative). 【Conclusion】 After long-term following up and repeated screening, we found that none of the OBI patients turned into acute or chronic HBV infection, and most of them maintained OBI.However, OBI blood donors carry very low load of HBV DNA for a long time, which could lead to false negative results of NAT and bring a great challenge to the safety of blood transfusion.
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Objective@#To analyze the residual risk of transfusion transmitted hepatitis B virus (HBV) infection by enzyme-linked immunosorbent assay (ELISA) method in hepatitis B surface antigen (HBsAg) negative blood donors, and to assess the infection status.@*Methods@#A total of 45551 samples were collected from blood donors.All samples were tested by 2 different ELISA kids of HBsAg and nucleic acid testing (NAT) individually of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Those ELISA HBsAg negative and NAT single reactive (HBsAg-/HBV DNA+ ) specimens were analyzed by quantitative detection of HBV DNA and by serologic testing of HBV antigen and antibody.@*Results@#A total of 44 HBsAg-/HBV DNA+ samples were detected, including 42 occult HBV infections (OBI) and 2 window period infections (WP). The detection rate of OBI rate was 0.90‰, and 32 samples of OBI sample HBV DNA was less than 20 IU/ml, and the OBI detection rate was significantly different between different genders, ages and blood donation times (P<0.05). In the OBI sample, there were 6 serological models, 92.9%(39/42) OBI samples hepatitis B core antibody (HBcAb) positive, and 76.9%(30/39) HBV DNA in HBcAb positive samples were less than 20 IU/ml; 29.5% (13/42) of OBI blood donors hepatitis B e antigen (HBeAb) and HBcAb were also positive, of whom 84.6% (11/13) were HBV DNA quantitatively <20 IU/ml.@*Conclusions@#HBV residual risk of transfusion-transmitted infection may occur through HBsAg- and single NAT reactive blood donors, mainly include OBI, and HBV DNA low level. Blocking of single NAT reactive blood donors could reduce transfusion-transmitted HBV infection.
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The level of viral DNA in patients with occult hepatitis B virus infection (OBI) is very low, and it is difficult to detect the conventional serum marker-HBsAg. OBI brought challenges to the clinical diagnosis and treatment and blood transfusion safety. The mechanism involved in OBI and the clinical implication are getting more and more attention. OBI has a complex mechanism that may involve host factors, the virus itself, and other viral or nonviral factors. OBI has the risk of HBV transmission. HBV can be reactivated and the liver disease can be aggravated in patients with OBI.
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Occult hepatitis B virus infection is a worldwide public health problem,which seriously affects the clinical diagnosis of hepatitis B and threatens the safety of blood transfusion.The concept of occult hepatitis B virus infection,the pathogenesis of occult hepatitis B virus infection,the prevalence of occult hepatitis B virus infection in different groups,including healthy population and different patients,and the possibility of transmission were summarized.The prevalence of occult hepatitis B virus infection was found in healthy population and different patients,and there is possibility of occult hepatitis B virus infection to be transmitted through blood transfusion.The paper provides a comprehensive introduction of the pathogenesis and prevalence of occult hepatitis B virus infection.More attention should be paid to occult hepatitis B virus infection.
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Occult hepatitis B virus infection is a worldwide public health problem,which seriously affects the clinical diagnosis of hepatitis B and threatens the safety of blood transfusion.The concept of occult hepatitis B virus infection,the pathogenesis of occult hepatitis B virus infection,the prevalence of occult hepatitis B virus infection in different groups,including healthy population and different patients,and the possibility of transmission were summarized.The prevalence of occult hepatitis B virus infection was found in healthy population and different patients,and there is possibility of occult hepatitis B virus infection to be transmitted through blood transfusion.The paper provides a comprehensive introduction of the pathogenesis and prevalence of occult hepatitis B virus infection.More attention should be paid to occult hepatitis B virus infection.
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Objective To study the prevalence of the occult hepatitis B virus infection (OBI) and the mutation of amino acid sequence in S gene of voluntary blood donors in AnHui/FuJian/Jiang Xi Province Blood centers.Methods Serologic testing for anti-HBc by ELISA was performed with HBsAg-HBV DNA+ samples from voluntary blood donors in three province blood centers.The S region of HBV of those samples was amplified and sequenced.The genotype and mutation of amino acid sequence were analyzed by MEGA6.Results 21 in 123046 blood donors from AnHui Province blood center were HBsAgHBV DNA+,the prevalence of OBI was 0.017％,and 76.2％ of these-OBI samples was positive in anti-HBc,S region was amplified by nest-PCR in 15 OBI samples,8 of them were B genotype,the others were C genotype.39 samples of 51 OBI blood donors from FuJian Province blood center were anti-HBc positive,16 samples of those OBI donors were amplified S region,14 were B genotype,the others were C genotype.There are 30 OBI blood donors from JiangXi Province blood center,24 of them were anti-HBc positive,S region was amplified in 4 samples,1 was B genotype,the others were C genotype.Of all 35 OBI samples,26 showed amino acid mutation,which was in MHR region of S gene,especially in HBV α epitope.Conclusion The rate of prevalence of OBI in AnHui Province was 0.017％,there was also certain OBI infection in FuJian and JiangXi Province.In the OBI samples which were amplified S region,the positive rates of anti-HBc in three blood centers were 73.3％,93.8％,100％.B Genotype was the main HBV genotype.The mutation in MHR region of S gene,especially in HBV α epitope,may be one of the reasons to cause OBI.
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Objective To analyze the mutation of PreS-S region in occult hepatitis B virus(OHBV) in HBV infected persons with positive HBsAb and investigate the biological mechanisms of the special infectious model.Methods A total of 38 HB-sAb positive OBI serum samples were amplified by Nested PCR and sequenced,HBV genotype and serotype were determined.The amino acid sequences of OHBV were compared to the corresponding sequence of wild-type strains of similar genotype obtained from the GenBank database.Results PreS-S segment of 11 samples were obtained and 8 samples were sequenced successfully.Among which,5 were genotype C and 3 were genotype B.Genotype B were all serotype adw,while genotype C were 1 adw and 4 adr.The mutation rates of PreS-S region,the immunoreactive area and the major hydrophilic region (MHR) were higher in OHBV than the wild-type strains (2.6％ vs 0.8％,x2 =40.23,3.2％ vs 0.3％,x2 =52.13,3.6％ vs 0.6％,x2 =13.25,all P＜0.01) and the substitutions of I126T,Q129R,M133T,F134I,D144E,G145K in α determinant were found in OBI samples.The mutation rate of amino acids in PreS-S region was higher in genotype C than genotype B (3.5％ vs 1.2％,x2--15.98,P＜0.01),meanwhile,the mutation rates in MHR,α determinant and immunoreactive region were higher in genotype C too,but no statistical significance was attained (4.7％ vs 1.7 ％,x2 =2.96,3.6 ％ vs 2.9％,x2 =0.25,4.1％ vs 2.3％,x2 =3.59,all P ＞0.05).Conclusion Mutations in PreS-S region,especially in immunoepitope,might change the virus'immunogenicity leading to escape from immune response and cause OBI with HBsAb positive.
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Objective To research and analyze serological and virological epidemiology charactererization of occult hepatitis B virus infection in Jiaxing volunteer blood donors.Methods 52 698 samples were screened by ELISA(HBsAg、antiHCV 、anti-HIV、anti-TP) and Nucleic acid amplification technique(NAT),then NAT positive samples were further identified to detect virus type.HBsAg-/HBV-DNA+ samples were collected in three different kinds of qualitative HBsAg detection of ELISA kit.The quantitative determination of HBsAg and anti-HBs were used by chemiluminescencemethod.At the same time,real-time fluorescence quantitative PCR (QPCR) was used to measure the viral load of HBV.Further analysis and study on the serological and virological distribution of OBI combined with five markers of hepatitis B virus (HBV),with tracing general epidemiological data (sex,age and age).Results The prevalence rate of OBI was 0.89‰ (1 ∶ 1 121) in all donors with OBI infection,and 2 cases of window period (WP) were found in 52698 donors (1 ∶ 26 349).The results of HBsAg and HBeAg were negative in 49 HBsAg-/HBV-DNA+ samples,and 6OBI serological profiles were found.Anti-HBs quantitative concentration(＞100 mIU/mL)accounted for 27.66％ (13/47),while anti-HBc+ positive rate was 91.49％ (43/47).HBV-DNA nucleic acid quantitative ranged from 4.10 to 1.82× 103(IU/mL) (median of 15.83),whereas HBsAg+/HBV-DNA+positive viral load was in the range of 61.47 to 1.28× 104(IU/mL) (median of 538.15).The difference was significant in viral load between experiment group and control group(P＜0.05).Male donors of more than 40 years were higher in prevalence rate of OBI infection (P＜0.05),meanwhile there was a significant difference in OBI infection rate between repeated blood donors and fnrst blood donors(0.01＜P＜0.05).Conclusion The viral load was low in OBI infected donors,and anti-HBc+ was the main manifestation.NAT had the ability to detect OBI,shorten the window period,and contributed to ensure the safety of clinical blood.
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Objective To explore the biological and serological characteristics of occult HBV infection among qualified young blood donors with anti-HBc positive in Suzhou area .Methods 120 young blood donors with negative HBsAg and reactivity in NAT in our hospital from October 2013 to June 2016 were selected as the research subjects .The anti-HBs quantitative detection and two pairs of semi-hepatitis B detection were performed .The samples of anti-HBc positive were conducted the viral nucleic acid extraction and nested PCR at the basic core promoter(BCP) region ,pre-core(PC) region and S region .The samples with positive amplification results were performed the gene sequencing and sequential analysis .Results Among 120 volunteer blood donors ,anti-HBc(+ ) had 31 cases ,in which 25 cases were in the 22-25 years old group and 6 cases in the 18-21 years old group ,the difference was statisti-cally significant(P<0 .05);anti-HBs(+ ) had 89 cases ,among them ,16 cases were in the 22 -25 years old group and 73 cases in the 18-21 years old group .The nest PCR was used to conduct PCR amplification in 31 samples of anti-HBc(+ ) ,in which 1 case was BCP region positive and 2 cases were S region positive ,all belonged to the 22-25 years old group .In the typing and sequencing for the samples of S region positive ,the results showed that all 2 cases were B type HBV .Compared with wild type DNA sequence , among them 1 cases had amino acid sequence E44U variation and 1 cases had T532G mutation .Conclusion For the anti-HBc(+ ) young blood donors qualified in HBsAg detection ,it is not guaranteed that their blood do not contain HBV DNA .It is still needed to further increase the sensitivity of nucleic acid detection method in hepatitis B highly prevalent areas fro decreasing the risk of HBV transmission by blood transfusion .
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Introducción: la infección oculta por el virus de la hepatitis B se caracteriza por la presencia en suero o plasma del genoma viral y anticuerpos contra la proteína de la cápsida (anti-HBc) en ausencia del marcador de infección.Objetivos: detectar la IOB en los pacientes hemodializados e identificar la posible relación de la IOB con la infección por el virus de la hepatitis C y variables sociodemográficas y epidemiológicas.Métodos: se estudiaron 709 muestras de pacientes provenientes de 18 unidades de hemodiálisis de Cuba. Se determinaron marcadores de infección, exposición e inmunidad al virus de la hepatitis B. Las muestras con HBsAg negativo, anti-HBc positivo y niveles de anti-HBs < 50 UI/L se les analizó la detección de ADN del virus de la hepatitis B y marcadores de lvirus de la hepatitis C.Resultados: las prevalencias de la infección y la exposición al virus de la hepatitis B fueron de 6,9 por ciento y 28,6 por ciento, respectivamente. El 4,3 por ciento de las muestras tuvieron criterio de infección oculta por el virus de la hepatitis B ; esta se detectó en el 58,1 por ciento (18/31) de los casos, con cargas virales menores de 105 UI/mL. La prevalencia global de infección oculta por el virus de la hepatitis B fue de 2,5 por ciento (18/709). No se encontró asociación significativa entre las variables analizadas.Conclusiones: la infección oculta por el virus de la hepatitis B fue frecuente en pacientes hemodializados con bajos niveles de anti-HBs, principalmente en aquellos con concentraciones no protectoras. Este estudio ratifica la necesidad de mantener la estrategia de prevención contra las hepatitis virales de transmisión parenteral en las unidades de diálisis(AU)
Introduction: occult hepatitis B virus infection is characterized by the presence of the viral genome and antibodies to the capside protein in serum or plasma (anti-HBc) that test negative for the infection marker.Objectives: to detect the occult hepatitis B virus in hemodialysis patients and to identify the possible relationship between occult hepatitis B infection and hepatitis C virus infection and the epidemiological and demographic variables.Methods: seventy thousand and nine serum samples from patients treated in 18 hemodialysis units were included. Serological markers for HBV infection, exposure and immunity were tested. Samples with negative HBsAg , positive anti-HBc and anti-HBs titers <50 IU/L were tested for detection of HBV-DNA and HCV markers.Results: the prevalence of HBV infection and exposure were 6.9 percent and 28.6 percent respectively. In the group, 4.3 percent of samples met occult hepatitis B infection criteria, the HBV-DNA was detected in 58.1 percent (18/31) of the samples, with viral loads below 105 IU/mL. Overall occult hepatitis B infection prevalence was 2.5 percent (18/709). There was no significant association among the analyzed variables.Conclusions: occult hepatitis B infection was frequent in hemodialysis patients with low levels of anti-HBs mainly in those with non protected titers. This study supports the need of keeping the prevention strategies against parenterally transmitted viral hepatitis in dialysis units(AU)
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Humans , Hepatitis B virus/isolation & purification , Renal Dialysis/adverse effects , Hepatitis B/epidemiology , Epidemiology, Descriptive , Cross-Sectional Studies , Hepatitis C/blood , CubaABSTRACT
Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , DNA, Viral/isolation & purification , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/epidemiology , Liver Transplantation , Liver Cirrhosis/virology , Asymptomatic Infections/epidemiology , Biomarkers , Brazil/epidemiology , Carcinoma, Hepatocellular/complications , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Hepatitis, Chronic/complications , Hepatitis, Chronic/epidemiology , Liver Neoplasms/complications , Polymerase Chain Reaction , Prevalence , Tertiary Care CentersABSTRACT
Occult HBV infection is characterized by the absence of serum HBsAg with persistence of low level of intrahepatic HBV DNA. Several suggested mechanisms for the origin of occult HBV infection include strong suppression of viral replication and gene expression, mutation in the regulatory regions of HBV genome, formation of immunoglobulin-bound HBsAg, viral interference, and blockage of HBsAg secretion from infected hepatocytes. Standardized assays are not yet available, and sensitive HBV DNA amplification assay is necessary for the diagnosis of cryptic infection. Detection rate of HBV DNA is highest in IgG anti-HBc positive population. However, neither anti-HBc nor anti-HBs can be detected in a significant proportion of infected persons. Occult HBV infection occurs in a number of clinical settings and is highly prevalent in HCV-infected patients as well as in patients with cryptogenic chronic liver disease including hepatocellular carcinoma.
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Humans , DNA, Viral/analysis , Hepatitis B/diagnosis , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/bloodABSTRACT
Many studies have suggested that occult HBV infection has a substantial clinical relevance to hepatocellular carcinoma (HCC). Occult HBV infection is an important risk factor for the development of cirrhosis and HCC in patients without HBsAg. As a matter of fact, occult HBV infection is one of the most common causes of crytogenic HCC in endemic areas of HBV. However, there still are controversial issues about the association between occult HBV infection and HCC according to the underlying liver disease. In alcoholic cirrhosis, occult HBV infection may exert synergistic effect on the development of HCC. However, there is insufficient evidence to relate occult HBV infection to hepatocarcinogenesis in non-alcoholic fatty liver disease. In cryptogenic HCC, occult HBV infection may play a direct role in the development of HCC. In order to elucidate the assocciation between occult HBV infection and HCC, underlying liver disease must be specified and larger number of cases must be included in future studies.
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Humans , Carcinoma, Hepatocellular/complications , DNA, Viral/analysis , Hepatitis/complications , Hepatitis B/complications , Hepatitis B virus/genetics , Liver Cirrhosis, Alcoholic/complications , Liver Neoplasms/complications , Risk FactorsABSTRACT
Objective Prevalence of occult hepatitis B virus (HBV) infection (OBI) was investigated in a paired mother-teenager population and HBV S gene variation including overt and occult HBV,was determined.Methods A follow-up study based on an initial survey of 135 mother-teenager pairs was carried out through collection of questionnaires and blood samples HBsAg were detected by ELISA method,viral load by PCR amplification and HBV S gene by phylogenetic analysis.Results 102 pairs of subjects were followed-up.Blood samples from 94 mothers and 101children were collected.OBI prevalence in mothers was 10.0％ (6/60),significantly higher than 2.0％(2/101) in teenagers.Medians of viral load were 399.9 IU/ml and 247.6 IU/ml in overt and occult HBV strains,but without significant difference.1 occult HBV strain belonged to genotype B with serotype adw while the other 7 were genotype C with serotype adr.15 of the overt HBV strains belonged to genotype B with serotype adw and the other 8 were genotype C with serotype adr.Proportions of genotype-C strains were significantly higher in occult HBV strains than in overt HBV strains.Conclusion OBI was seen in teenage-mother population.
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A 60-year-old woman with end stage liver cirrhosis caused by genotype 2 hepatitis C virus (HCV) infection received an orthotopic liver transplantation (OLT). The patient was negative for the hepatitis B surface antigen (HBsAg) and positive for the anti-hepatitis B surface antibody (anti-HBs) prior to and one and a half months following the OLT. Due to reactivation of hepatitis C, treatment with interferon-alpha and Ribavirin started two months following the OLT and resulted in a sustained virological response. We performed a liver biopsy because a biochemical response was not achieved. Surprisingly, liver pathology showed HBsAg-positive hepatocytes with a lobular hepatitis feature, which had been negative in the liver biopsy specimen obtained one and a half months post-OLT. High titers of both HBsAg and HBeAg were detected, while anti-HBs antibodies were not found. Tests for IgM anti-hepatitis B core antibody and anti-delta virus antibodies were negative. The serum HBV DNA titer was over 1x10(7) copies/mL. A sequencing analysis showed no mutation in the "a" determinant region, but revealed a mixture of wild and mutant strains at an overlapping region of the S and P genes (S codon 213 (Leu/Ile); P codons 221 (Phe/Tyr) and 222 (Ala/Thr)). These findings suggest that de novo hepatitis B can develop in patients with HCV infection during the post-OLT period despite the presence of protective anti-HBs.
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Female , Humans , Middle Aged , Antibodies , Biopsy , Codon , DNA , Genotype , Hepacivirus , Hepatitis , Hepatitis B , Hepatitis B e Antigens , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis C , Hepatocytes , Immunoglobulin M , Interferon-alpha , Liver , Liver Cirrhosis , Liver Transplantation , Ribavirin , Superinfection , VirusesABSTRACT
BACKGROUND: We investigated hepatitis B virus (HBV) infection cases, who were HBsAg negative by radioimmunoassay (RIA) and HBV DNA positive for their clinical characteristics, the S gene mutation of hepatitis B virus (HBV), and usefulness of other HBsAg immunoassay. METHODS: Among the patients requested for HBV DNA quantification, 16 patients positive in HBV DNA but negative in HBsAg RIA (BNIBT HBsAg Kit, China) were enrolled. The "a" determinant of HBV S gene was sequenced and clinical characteristics were reviewed. Additional HBsAg assay was performed using Architect HBsAg kit (Abbott laboratories, USA) employing chemiluminescent immunoassay method. RESULTS: Eleven of the 16 patients showed multiple mutations in the "a" determinant. These patients received liver transplantation several years ago and have been treated with hepatitis B immune globulin (HBIG) and antiviral drugs. G145R mutation was found in 8 patients and G145K, D144G, and D144A were also frequently found. Among 9 of the 11 patients tested for HBsAg by Architect HBsAg kit, 8 showed positive results. Among 4 of the remaining 5 patients, only 2 showed weak positive results (< or =1 IU/mL) in Architect HBsAg kit. CONCLUSIONS: HBV DNA-positive/HBsAg RIA-negative results were mostly observed in the patients treated with HBIG after liver transplantation, in whom HBIG escape mutations were found. Majority of these cases were positive in Architect HBsAg assay, and it is recommended to use other HBsAg immunoassay methods that are more sensitive than RIA in the detection limit as well as in the detection of escape mutant in hospitals performing liver transplantation.